The Immunology of COVID-19

Question 1

SARS-CoV-2 and related viruses: SARS and common cold

Answer 1

Question 2

SARS-CoV-2 is a …-sense, …-stranded RNA virus

Answer 2

SARS-CoV-2 is a positive-sense, single-stranded RNA virus

Question 3

SARS-CoV-2 and related viruses: basics

• SARS-CoV-2 is a …-sense, single-stranded … virus
• Infects … and …
• Replication and gene expression occurs in the … of the host cell
• Can use … cell proteins during replication and gene expression
• Express … proteins separately from non-… ones
• … proteins are expressed from a set of subgenomic mRNAs (require replication for expression)

Answer 3

• SARS-CoV-2 is a positive-sense, single-stranded RNA virus
• Infects vertebrates and invertebrates
• Replication and gene expression occurs in the cytoplasm of the host cell
• Can use host cell proteins during replication and gene expression
• Express structural proteins separately from non-structural ones
• Structural proteins are expressed from a set of subgenomic mRNAs (require replication for expression)

Question 4

SARS-CoV-2 and related viruses: basics

• SARS-CoV-2 is a positive-sense, single-stranded RNA virus
• Infects vertebrates and invertebrates
• … and … expression occurs in the cytoplasm of the host cell
• Can use host cell proteins during … and … expression
• Express structural proteins … from non-structural ones
• Structural proteins are expressed from a set of … mRNAs (require replication for expression)

Answer 4

• SARS-CoV-2 is a positive-sense, single-stranded RNA virus
• Infects vertebrates and invertebrates
• Replication and gene expression occurs in the cytoplasm of the host cell
• Can use host cell proteins during replication and gene expression
• Express structural proteins separately from non-structural ones
• Structural proteins are expressed from a set of subgenomic mRNAs (require replication for expression)

Question 5

SARS-CoV-2 and related viruses: cell entry

Answer 5

Question 6

SARS-CoV-2 and related viruses: cell/tissue tropism

• Tissue tropism is largely determined by … expression
  
  • In most tissues, what cells are infected? (2)

Answer 6

• Tissue tropism is largely determined by ACE2 expression
• In most cells - EC and VEC INFECTED
  
  • Lungs: basal ciliated and club cells, proliferative EC1, AT2 cells2, VEC3
  • Trachea: ciliated and goblet cells of mucosa, EC of conduits and glands
  • Intestines: EC in mucosa and glands
  • Skin: secretory luminal cells in sweat glands, VEC
  • Kidneys: EC in the distal tubule and collecting ducts, VEC
  • Pancreas: EC in Langerhans glands and intra-islet ducts, VEC
  • Brain: VEC
  • Heart: VEC
    
    • 1EC=epithelial cell, 2AT2 =alveolar type 2 cell, 3VEC=vascular endothelial cell

Question 7

SARS-CoV-2 and related viruses: target tissues and symptoms

• Important target tissues
  
  • Lung – … (pneumonia)
  • Vasculature – … (contributing to thrombotic events)
  • Gut – epithelial cells, lymphocytes (…, pain, loos of …)
  • CNS – vasculitis (C…)
  • Muscle – fatigue/weakness, M…
  • Naso and oropharynx (sensory neuroepithelium) – loss of … and …

Answer 7

• Important target tissues
  
  • Lung – pneumocytes (pneumonia)
  • Vasculature – vasculitis (contributing to thrombotic events)
  • Gut – epithelial cells, lymphocytes (diarrhea, pain, loos of appetite)
  • CNS – vasculitis (confusion)
  • Muscle – fatigue/weakness, myalgia
  • Naso and oropharynx (sensory neuroepithelium) – loss of smell and taste

Question 8

SARS-CoV-2 and related viruses: target tissues and symptoms

• Important target tissues
  
  • … – pneumocytes (pneumonia)
  • … – vasculitis (contributing to thrombotic events)
  • … – epithelial cells, lymphocytes (diarrhea, pain, loos of appetite)
  • … – vasculitis (confusion)
  • … – fatigue/weakness, myalgia
  • … and … (sensory neuroepithelium) – loss of smell and taste

Answer 8

• Important target tissues
  
  • Lung – pneumocytes (pneumonia)
  • Vasculature – vasculitis (contributing to thrombotic events)
  • Gut – epithelial cells, lymphocytes (diarrhea, pain, loos of appetite)
  • CNS – vasculitis (confusion)
  • Muscle – fatigue/weakness, myalgia
  • Naso and oropharynx (sensory neuroepithelium) – loss of smell and taste

Question 9

SARS-CoV-2 and related viruses: infection in animals

• Coronaviruses may infect a wide variety of animals, both terrestrial and aquatic, domestic and wild.

Answer 9

• Coronaviruses may infect a wide variety of animals, both terrestrial and aquatic, domestic and wild.

Question 10

SARS-CoV-2 and related viruses: animals

• Horseshoe bats harbour the bat coronavirus RaTG13 which exhibits 97.4% amino acid identity with SARS-CoV-2 in the Spike protein
• But bats don’t seem to get sick from coronaviruses
• Bats have … body temperature of about 39 C (related to heir ability to fly), this might work a bit like a …
• They also have a … in STING (Stimulator of Interferon Genes). This is the main adaptor in several DNA-sensing pathways. The … makes it less potent, so that less … is being produced.
• This reduces …

Answer 10

• Horseshoe bats harbour the bat coronavirus RaTG13 which exhibits 97.4% amino acid identity with SARS-CoV-2 in the Spike protein
• But bats don’t seem to get sick from coronaviruses
• Bats have higher body temperature of about 39 C (related to heir ability to fly), this might work a bit like a fever.
• They also have a mutation in STING (Stimulator of Interferon Genes). This is the main adaptor in several DNA-sensing pathways. The mutation makes it less potent, so that less interferon is being produced.
• This reduces inflammation

Question 11

SARS-CoV-2 and related viruses: animals

• Horseshoe bats harbour the bat coronavirus RaTG13 which exhibits 97.4% amino acid identity with SARS-CoV-2 in the Spike protein
• But bats don’t seem to get … from coronaviruses
• Bats have higher body temperature of about … C (related to heir ability to fly), this might work a bit like a fever.
• They also have a mutation in S…. This is the main adaptor in several DNA-sensing pathways. The mutation makes it less potent, so that less interferon is being produced.
• This reduces inflammation

Answer 11

• Horseshoe bats harbour the bat coronavirus RaTG13 which exhibits 97.4% amino acid identity with SARS-CoV-2 in the Spike protein
• But bats don’t seem to get sick from coronaviruses
• Bats have higher body temperature of about 39 C (related to heir ability to fly), this might work a bit like a fever.
• They also have a mutation in STING (Stimulator of Interferon Genes). This is the main adaptor in several DNA-sensing pathways. The mutation makes it less potent, so that less interferon is being produced.
• This reduces inflammation

Question 12

Genome structure & protein expression

• The genome translates into about … expressed proteins. Major proteins are
  
  • The … protein or (S-protein)
  • The … (E) protein
  • The … protein (M-protein) and
  • The … protein (N-protein)
  • The size of the genome is about 30kb (HIV 9.2 kb, CMV 230 kb)
  • Total protein length in amino acids is about …

Answer 12

• The genome translates into about 30 expressed proteins. Major proteins are
  
  • The spike protein or (S-protein)
  • The envelope (E) protein
  • The membrane protein (M-protein) and
  • The nucleocapsid protein (N-protein)
  • The size of the genome is about 30kb (HIV 9.2 kb, CMV 230 kb)
  • Total protein length in amino acids is about 9000

Question 13

Genome structure & protein expression

• List of SARS-CoV-2 proteins/size
• Size corresponds to the relative number of potential …-cell and …-cell …

Answer 13

• List of SARS-CoV-2 proteins/size
• Size corresponds to the relative number of potential B-cell and T-cell epitopes

Question 14

Genome structure & protein expression

• The spike protein has 2 subunits, … and …
• The … subunit contains a receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2
• … subunit mediates viral cell membrane fusion

Answer 14

• The spike protein has 2 subunits, S1 and S2
• The S1 subunit contains a receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2
• TheS2 subunit mediates viral cell membrane fusion

Question 15

General interaction with the immune system: overview (COVID-19)

Answer 15

Question 16

… immunity is our first line defence against pathogens and its proper functioning may be a crucial contributor to … courses of COVID-19.

Answer 16

Innate immunity is our first line defence against pathogens and its proper functioning may be a crucial contributor to asymptomatic courses of COVID-19.

Question 17

Innate immunity is our first line defence against pathogens and its proper functioning may be a crucial contributor to asymptomatic courses of COVID-19

• Is there a way of improving innate immunity?

Answer 17

There is no classic memory by way or training cells with specific receptors but ‘trained immunity’ has been described:

Question 18

Innate Immunity: How can it be trained?

Answer 18

Question 19

Trained immunity is the result of ‘firing up’ immunity by stimuli/events that stimulate the same … immune cells that are required to protect us from …

Answer 19

Trained immunity is the result of ‘firing up’ immunity by stimuli/events that stimulate the same innate immune cells that are required to protect us from infection

• This could be recent vaccination even if completely unrelated to the infectious agent that is dealt with more effectively as a result
• It could also be the result of a recent infection
• It may be achievable by vaccine adjuvants alone or by other substances like plant lectins.
• The fact that in older people innate immunity is often reduced may be one reason why older people are more likely to have severe COVID-19
• Some researchers suggested using the TB vaccine to protect against COVID-19. This is not completely implausible, but we now have better ways of vaccinating)

Question 20

Trained Immunity

• Trained immunity is the result of ‘firing up’ immunity by stimuli/events that stimulate the same innate immune cells that are required to protect us from infection
• This could be recent … even if completely unrelated to the infectious agent that is dealt with more effectively as a result
• It could also be the result of a recent …
• It may be achievable by vaccine … alone or by other substances like plant …
• The fact that in older people innate immunity is often … may be one reason why … people are more likely to have … COVID-19
• Some researchers suggested using the … vaccine to protect against COVID-19. This is not completely implausible, but we now have better ways of vaccinating)

Answer 20

• Trained immunity is the result of ‘firing up’ immunity by stimuli/events that stimulate the same innate immune cells that are required to protect us from infection
• This could be recent vaccination even if completely unrelated to the infectious agent that is dealt with more effectively as a result
• It could also be the result of a recent infection
• It may be achievable by vaccine adjuvants alone or by other substances like plant lectins.
• The fact that in older people innate immunity is often reduced may be one reason why older people are more likely to have severe COVID-19
• Some researchers suggested using the TB vaccine to protect against COVID-19. This is not completely implausible, but we now have better ways of vaccinating)

Question 21

B-cells and antibodies: blocking entry

Answer 21

Question 22

B-cells and antibodies: timeline

“Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France”​

• 90% … Ab 2-3 weeks after onset of symptom, almost all 4 weeks after
• … made later

Answer 22

• 90% IgM Ab 2-3 weeks after onset of symptom, almost all 4 weeks after
• IgG made later

Question 23

B-cells and antibodies: IgM / IgG

• Consistent antibody responses are detectable to the spike protein S… subunit and … protein throughout

Answer 23

• Consistent antibody responses are detectable to the spike protein S2 subunit and N protein throughout

Question 24

B-cells and antibodies: protective efficacy

• A study in health care workers in 2020 provided an estimate of protection by antibodies over 7 months. 12541 individuals were tested at baseline.
• Of 11364 individuals (90.6%) who were seronegative for anti-spike antibody at baseline
  
  • 88 converted to seropositive during the study
  • Their risk was estimated to be 0.60 per 10,000 days at risk
• Of 1177 (9.4%) who were seropositive for anti-spike antibody at baseline.
  
  • 2 were reinfected during the study (new positive PCR)
  • Their overall risk was estimated at 0.13 per 10,000 days at risk
• Following adjustment for covariates, an incidence rate ratio (IRR) of 0.11 was calculated. This translated into an efficacy of ..%.

Answer 24

• A study in health care workers in 2020 provided an estimate of protection by antibodies over 7 months. 12541 individuals were tested at baseline.
• Of 11364 individuals (90.6%) who were seronegative for anti-spike antibody at baseline
  
  • 88 converted to seropositive during the study
  • Their risk was estimated to be 0.60 per 10,000 days at risk
• Of 1177 (9.4%) who were seropositive for anti-spike antibody at baseline.
  
  • 2 were reinfected during the study (new positive PCR)
  • Their overall risk was estimated at 0.13 per 10,000 days at risk
• Following adjustment for covariates, an incidence rate ratio (IRR) of 0.11 was calculated. This translated into an efficacy of 89%.

Question 25

For vaccines, vaccine efficacy (VE) can be calculated in the same way:

Answer 25

VE = 1 – (IRvaccinated/IRnon-vaccinated)=1-IRR

Question 26

B-cells and antibodies: neutralising titres

• Determining neutralising antibody titres requires an … system that allows precise detection of infection relative to … levels.

Answer 26

• Determining neutralising antibody titres requires an experimental system that allows precise detection of infection relative to antibody levels.

Question 27

B-cells and antibodies: timeline of decay

• Immunological memory to SARS-CoV-2 assessed for up to … months after infection
• Longitudinal data on neutralising antibody titres (serum dilutions) shows a … of neutralising capacity and allows an estimate of the duration of protection if the levels required for protection are know.

Answer 27

• Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection
• Longitudinal data on neutralising antibody titres (serum dilutions) shows a decline of neutralising capacity and allows an estimate of the duration of protection if the levels required for protection are know.

Question 28

B-cells and antibodies: time-line of decay

• “Neutralizing antibody levels are … predictive of immune protection from … SARS-CoV-2 infection”

Answer 28

“Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection”

Question 29

B-cells and antibodies: the concern with variants

• Mutations occur in all SARS-C0V-2 proteins, however, those in the … protein are most concerning because the development of therapeutics has -focused on the … protein. This is because the … protein is crucial for viral entry into cells.

Answer 29

• Mutations occur in all SARS-C0V-2 proteins, however, those in the Spike protein are most concerning because the development of therapeutics has -focused on the Spike protein. This is because the Spike protein is crucial for viral entry into cells.

Question 30

Mutations occur in all SARS-C0V-2 proteins, however, those in the Spike protein are most concerning because the development of … has -focused on the Spike protein. This is because the Spike protein is crucial for … … into cells.

Answer 30

Mutations occur in all SARS-C0V-2 proteins, however, those in the Spike protein are most concerning because the development of therapeutics has -focused on the Spike protein. This is because the Spike protein is crucial for viral entry into cells.

Question 31

B-cells and antibodies: recent rises in case numbers

• A large proportion of new cases are of the India variant
• It is estimated that 20,000 individuals arrived from India after the Indian variant (B.1.617) was first detected in the UK (The Times, 16 May 2021 ).
• This may explain why a large proportion of cases are now caused by this variant or sub-variants arising from it.
• The Indian variant appears easier to transmit, however, vaccines appear to work albeit with somewhat … efficacy
• The easing of lock-down, however, is likely to contribute to the recent increase in cases of whichever variant.

Answer 31

• A large proportion of new cases are of the Indian variant
• It is estimated that 20,000 individuals arrived from India after the Indian variant (B.1.617) was first detected in the UK (The Times, 16 May 2021 ).
• This may explain why a large proportion of cases are now caused by this variant or sub-variants arising from it.
• The Indian variant appears easier to transmit, however, vaccines appear to work albeit with somewhat lower efficacy
• The easing of lock-down, however, is likely to contribute to the recent increase in cases of whichever variant.

Question 32

B-cells and antibodies: recent rises in case numbers

• A large proportion of new cases are of the … variant
• It is estimated that 20,000 individuals arrived from … after the … variant (B.1.617) was first detected in the UK (The Times, 16 May 2021 ).
• This may explain why a large proportion of cases are now caused by this variant or sub-variants arising from it.
• The Indian variant appears easier to transmit, however, vaccines appear to work albeit with somewhat lower efficacy
• The easing of lock-down, however, is likely to contribute to the recent increase in cases of whichever variant.

Answer 32

• A large proportion of new cases are of the Indian variant
• It is estimated that 20,000 individuals arrived from India after the Indian variant (B.1.617) was first detected in the UK (The Times, 16 May 2021 ).
• This may explain why a large proportion of cases are now caused by this variant or sub-variants arising from it.
• The Indian variant appears easier to transmit, however, vaccines appear to work albeit with somewhat lower efficacy
• The easing of lock-down, however, is likely to contribute to the recent increase in cases of whichever variant.

Question 33

B-cells and antibodies: SARS-CoV-2 variants

Answer 33

Question 34

B-cells and antibodies: Therapeutics

• Therapeutic antibodies recognising the … protein are administered to individuals with COVID-19 to avoid serious disease courses.
• Treatment with …-COV2 resulted in a statistically significant reduction in the time-weighted average daily change from baseline in viral load (log10 copies/mL) from day 1 through day 7. T (European Medicines Agency, EMA/142650/2021)
• Can be given (also subcutaneously) to … … for protection. It reduced the rate of symptomatic infection by 81% between day 0 and 29.

Answer 34

• Therapeutic antibodies recognising the Spike protein are administered to individuals with COVID-19 to avoid serious disease courses.
• Treatment with REGN-COV2 resulted in a statistically significant reduction in the time-weighted average daily change from baseline in viral load (log10 copies/mL) from day 1 through day 7. T (European Medicines Agency, EMA/142650/2021)
• Can be given (also subcutaneously) to household members for protection. It reduced the rate of symptomatic infection by 81% between day 0 and 29.

Question 35

B-cells and antibodies: Therapeutics

• Therapeutic antibodies recognising the Spike protein are administered to individuals with COVID-19 to avoid serious disease courses.
• Treatment with REGN-COV2 resulted in a statistically significant reduction in the time-weighted average daily change from baseline in viral load (log10 copies/mL) from day … through day …. T (European Medicines Agency, EMA/142650/2021)
• Can be given (also subcutaneously) to household members for protection. It reduced the rate of symptomatic infection by …% between day 0 and 29.

Answer 35

• Therapeutic antibodies recognising the Spike protein are administered to individuals with COVID-19 to avoid serious disease courses.
• Treatment with REGN-COV2 resulted in a statistically significant reduction in the time-weighted average daily change from baseline in viral load (log10 copies/mL) from day 1 through day 7. T (European Medicines Agency, EMA/142650/2021)
• Can be given (also subcutaneously) to household members for protection. It reduced the rate of symptomatic infection by 81% between day 0 and 29.

Question 36

B-cells and antibodies: antibody persistence and antigen

• Continuous antibody production requires antigen …
• The … epithelium may act as a reservoir for SARS-CoV-2 (as in HIV)
• …-Symptoms occur in 30-70% of infections
• … infection associated with lower mortality (attenuating effect?)
• SARS-CoV-2 RNA is found in stools
• … infection may be self limiting (mostly no live virus isolated from stools)
• SARS-CoV-2 may affect and change the gut virome (reduced diversity) with wide-ranging effects on immunity and therapeutic potential
  
  • This is mostly uncharted territory……

Answer 36

• Continuous antibody production requires antigen persistence
• The gut epithelium may act as a reservoir for SARS-CoV-2 (as in HIV)
• GI-Symptoms occur in 30-70% of infections
• GI infection associated with lower mortality (attenuating effect?)
• SARS-CoV-2 RNA is found in stools
• GI infection may be self limiting (mostly no live virus isolated from stools)
• SARS-CoV-2 may affect and change the gut virome (reduced diversity) with wide-ranging effects on immunity and therapeutic potential
  
  • This is mostly uncharted territory……

Question 37

B-cells and antibodies: antibody persistence and antigen

• Continuous antibody production requires antigen persistence
• The gut epithelium may act as a reservoir for SARS-CoV-2 (as in HIV)
• GI-Symptoms occur in ..-..% of infections
• GI infection associated with … mortality (attenuating effect?)
• SARS-CoV-2 RNA is found in …
• GI infection may be self … (mostly no live virus isolated from stools)
• SARS-CoV-2 may affect and change the gut … (reduced diversity) with wide-ranging effects on immunity and therapeutic potential
  
  • This is mostly uncharted territory……

Answer 37

• Continuous antibody production requires antigen persistence
• The gut epithelium may act as a reservoir for SARS-CoV-2 (as in HIV)
• GI-Symptoms occur in 30-70% of infections
• GI infection associated with lower mortality (attenuating effect?)
• SARS-CoV-2 RNA is found in stools
• GI infection may be self limiting (mostly no live virus isolated from stools)
• SARS-CoV-2 may affect and change the gut virome (reduced diversity) with wide-ranging effects on immunity and therapeutic potential
  
  • This is mostly uncharted territory……

Question 38

The gut epithelium may act as a … for SARS-CoV-2 (as in HIV)

Answer 38

The gut epithelium may act as a reservoir for SARS-CoV-2 (as in HIV)

Question 39

COVID-19 / GI

• The gut … may act as a reservoir for SARS-CoV-2 (as in HIV)
• GI-Symptoms occur in …-…% of infections
• GI infection associated with lower … (attenuating effect?)
• SARS-CoV-2 RNA is found in …
• GI infection may be … … (mostly no live virus isolated from stools)
• SARS-CoV-2 may affect and change the gut … (reduced diversity) with wide-ranging effects on immunity and … potential

Answer 39

• The gut epithelium may act as a reservoir for SARS-CoV-2 (as in HIV)
• GI-Symptoms occur in 30-70% of infections
• GI infection associated with lower mortality (attenuating effect?)
• SARS-CoV-2 RNA is found in stools
• GI infection may be self limiting (mostly no live virus isolated from stools)
• SARS-CoV-2 may affect and change the gut virome (reduced diversity) with wide-ranging effects on immunity and therapeutic potential

Question 40

T-cells: basics (reminder)

• Conventional, alpha/beta T-cells are involved in immune response … and … of infected cells (they are your ‘standard’ CD4 and CD8 T-cells)
• They are essential for the defence against … and other intracellular agents
• The majority of T-cells is thought to be in the …
• There are many unconventional T-cells and a whole spectrum of T-cells that are increasingly innate-like (discussing these is beyond the scope of this lecture, we mention them in the mucosal immunology lecture)

Answer 40

• Conventional, alpha/beta T-cells are involved in immune response coordination and killing of infected cells (they are your ‘standard’ CD4 and CD8 T-cells)
• They are essential for the defence against viruses and other intracellular agents
• The majority of T-cells is thought to be in the gut
• There are many unconventional T-cells and a whole spectrum of T-cells that are increasingly innate-like (discussing these is beyond the scope of this lecture, we mention them in the mucosal immunology lecture)

Question 41

T-cells: proteins, peptides, epitopes

• Conventional CD4 and CD8 T-cells recognise antigenic … in the context of class-II and class-I … molecules, respectively (’epitopes’)
• The … locus is our most polymorphic gene locus (diversity supporting survival)
• SARS-CoV-2 provides a multitude of potentially recognised … that could be useful in testing and vaccines. Testing all of these would be … and labour …
• … prediction (although not perfect yet) followed by testing of selected peptides is increasingly becoming the industry standard

Answer 41

• Conventional CD4 and CD8 T-cells recognise antigenic peptides in the context of class-II and class-I MHC molecules, respectively (’epitopes’)
• The MHC locus is our most polymorphic gene locus (diversity supporting survival)
• SARS-CoV-2 provides a multitude of potentially recognised peptides that could be useful in testing and vaccines. Testing all of these would be costly and labour intensive.
• Epitope prediction (although not perfect yet) followed by testing of selected peptides is increasingly becoming the industry standard

Question 42

T-cells: proteins, peptides, epitopes

• Conventional CD4 and CD8 T-cells recognise antigenic peptides in the context of class-… and class-… MHC molecules, respectively (’epitopes’)
• The MHC locus is our most … gene locus (diversity supporting survival)
• SARS-CoV-2 provides a multitude of potentially recognised peptides that could be useful in testing and vaccines. Testing all of these would be costly and labour intensive.
• Epitope … (although not perfect yet) followed by testing of selected peptides is increasingly becoming the industry standard

Answer 42

• Conventional CD4 and CD8 T-cells recognise antigenic peptides in the context of class-II and class-I MHC molecules, respectively (’epitopes’)
• The MHC locus is our most polymorphic gene locus (diversity supporting survival)
• SARS-CoV-2 provides a multitude of potentially recognised peptides that could be useful in testing and vaccines. Testing all of these would be costly and labour intensive.
• Epitope prediction (although not perfect yet) followed by testing of selected peptides is increasingly becoming the industry standard

Question 43

T-cells: the search for the best target proteis/epitopes

• Some peptides recognised by T-cells in SARS-CoV-1 infection, the infection causing the 2002/2003 SARS epidemic, were identified in the past
• Some of them occur … in SARS-CoV-2
• There also is some homology between the … … coronaviruses (OC43, E229, NL63, HKU1) and SARS-CoV-2

Answer 43

• Some peptides recognised by T-cells in SARS-CoV-1 infection, the infection causing the 2002/2003 SARS epidemic, were identified in the past
• Some of them occur identically in SARS-CoV-2
• There also is some homology between the common cold coronaviruses (OC43, E229, NL63, HKU1) and SARS-CoV-2

Question 44

T-cells: recognition of SARS-CoV-2 peptide pools

• CD4 T-cells recognise essentially … SARS-CoV-2 proteins.
• … differences between unexposed and exposed individuals were found for spike, NCAP, VME, VEMP, ORF3b, and NSP3a

Answer 44

• CD4 T-cells recognise essentially all SARS-CoV-2 proteins.
• Significant differences between unexposed and exposed individuals were found for spike, NCAP, VME, VEMP, ORF3b, and NSP3a

Question 45

T-cells: CD8 T-cell responses peak around day 30
and … over time (COV-19)

Answer 45

T-cells: CD8 T-cell responses peak around day 30
and decline over time (COV-19)

Question 46

T-cells: CD8 T-cell responses peak around day 30
and … over time (COV-19)

Answer 46

T-cells: CD8 T-cell responses peak around day 30
and decline over time (COV-19)

Question 47

T-cells: immunity over time

• So far, follow-up has been too short to provide definite answers on the decline of T-cell immunity over time. It is normal for T-cell responses (like antibody responses) to … over time.
• … T-cell remain and will respond quickly if there is a new infection
• … levels of … T-cells are not known, this is an area that is not well understood with respect to any infection
• The most important T-cell … may be different in different individuals

Answer 47

• So far, follow-up has been too short to provide definite answers on the decline of T-cell immunity over time. It is normal for T-cell responses (like antibody responses) to contract over time.
• Memory T-cell remain and will respond quickly if there is a new infection
• Protective levels of memory T-cells are not known, this is an area that is not well understood with respect to any infection
• The most important T-cell targets may be different in different individuals

Question 48

T-cells: concerns about variants

• No evidence so far that variants critically affect T-cell …
• Large numbers of … appear to be recognised across all proteins with mutations unlikely to affect all epitopes
• Strong T-cell epitopes were found in the fusion peptide II (FP II) region of the … protein. FP II shows very little variation across strains of SARS-CoV-1/2, MERS and HCoVs indicating mutations may harm the virus
• T-cell … may be critical in preventing severe disease even if antibodies fail to prevent infection or cell-to-cell spread

Answer 48

• No evidence so far that variants critically affect T-cell immunity
• Large numbers of epitopes appear to be recognised across all proteins with mutations unlikely to affect all epitopes
• Strong T-cell epitopes were found in the fusion peptide II (FP II) region of the spike protein. FP II shows very little variation across strains of SARS-CoV-1/2, MERS and HCoVs indicating mutations may harm the virus
• T-cell responses may be critical in preventing severe disease even if antibodies fail to prevent infection or cell-to-cell spread

Question 49

T-cells: HLA-disease associations with respect to CoVID-19

• There is … evidence for associations of HLA-type and COVID-19 severity at this time
• Due to the huge … of the HLA locus, very large studies will be required in future to prove or disprove significant HLA-associations
• If found, such associations may inform vaccine strategies

Answer 49

• There is limited evidence for associations of HLA-type and COVID-19 severity at this time
• Due to the huge polymorphisms of the HLA locus, very large studies will be required in future to prove or disprove significant HLA-associations
• If found, such associations may inform vaccine strategies

Question 50

T-cells: HLA-disease associations with respect to CoVID-19

• There is limited evidence for associations of HLA-type and COVID-19 severity at this time
• Due to the huge polymorphisms of the HLA locus, very large studies will be required in future to prove or disprove significant HLA-associations
• If found, such associations may inform … strategies

Answer 50

• There is limited evidence for associations of HLA-type and COVID-19 severity at this time
• Due to the huge polymorphisms of the HLA locus, very large studies will be required in future to prove or disprove significant HLA-associations
• If found, such associations may inform vaccine strategies

Question 51

T-cells: HLA-disease associations with respect to CoVID-19

• HLA/Disease associations can be based on T-cell recognition of peptides presented by HLA-molecules
• May explain the role of biogeographical ancestry in disease …
• Recently published results suggest that the presence of HLA-A*0201 and HLA-A*0301 are associated with a … risk, but HLA-A*0101 with a … risk of death in older people (>60 years)

Answer 51

• HLA/Disease associations can be based on T-cell recognition of peptides presented by HLA-molecules
• May explain the role of biogeographical ancestry in disease susceptibility
• Recently published results suggest that the presence of HLA-A*0201 and HLA-A*0301 are associated with a lower risk, but HLA-A*0101 with a higher risk of death in older people (>60 years)

Question 52

Immunity in high-risk groups

• Some underlying diseases associated with fatal COVID-19 outcome may represent immunological risk factors, others simply weaken the patient
• 7 FACTORS - list

Answer 52

• Some underlying diseases associated with fatal COVID-19 outcome may represent immunological risk factors, others simply weaken the patient

Question 53

Immunity in high-risk groups

• Some underlying diseases associated with fatal COVID-19 outcome may represent immunological risk factors, others simply weaken the patient
• Fill in the blanks

Answer 53

• Some underlying diseases associated with fatal COVID-19 outcome may represent immunological risk factors, others simply weaken the patient

Question 54

Immunity in high-risk groups: immunology

• Some immunological aspects of known risk factors (work in progress)
  
  • …: reduced innate and adaptive immunity, reduced B-cell and T-cell receptor repertoires (‘immunosenescence’), thymic involution, fewer naïve T-cells, more memory T-cells
  • …: large numbers of pro-inflammatory cells in fatty tissue, increased leptin secretion promoting decreased numbers of regulatory T-cells and regulatory T-cell function
  • …: strongly glycosylated Ig are more pro-inflammatory
  • … disease: damaged endothelium (vasculopathy): risk of DIC and thrombotic events
  • … background: HLA-type, polymorphisms in genes regulating inflammation, vitamin D binding protein variants (e.g. less free Vit D in black people), vitamin D-deficiency, and many more

Answer 54

• Some immunological aspects of known risk factors (work in progress)
  
  • Age: reduced innate and adaptive immunity, reduced B-cell and T-cell receptor repertoires (‘immunosenescence’), thymic involution, fewer naïve T-cells, more memory T-cells
  • Obesity: large numbers of pro-inflammatory cells in fatty tissue, increased leptin secretion promoting decreased numbers of regulatory T-cells and regulatory T-cell function
  • Diabetes: strongly glycosylated Ig are more pro-inflammatory
  • Vascular disease: damaged endothelium (vasculopathy): risk of DIC and thrombotic events
  • Genetic background: HLA-type, polymorphisms in genes regulating inflammation, vitamin D binding protein variants (e.g. less free Vit D in black people), vitamin D-deficiency, and many more

Question 55

Immunity in high-risk groups: immunology

• Some immunological aspects of known risk factors (work in progress)
  
  • Age: reduced innate and adaptive immunity, reduced B-cell and T-cell receptor repertoires (‘immuno…’), thymic …, fewer … T-cells, more … T-cells
  • Obesity: large numbers of pro-… cells in fatty tissue, increased … secretion promoting decreased numbers of regulatory T-cells and regulatory T-cell function
  • Diabetes: strongly glycosylated I.. are more pro-inflammatory
  • Vascular disease: damaged … (vasculopathy): risk of DIC and thrombotic events
  • Genetic background: …-type, polymorphisms in genes regulating inflammation, vitamin D binding protein variants (e.g. less free Vit D in … people), vitamin …-deficiency, and many more

Answer 55

• Some immunological aspects of known risk factors (work in progress)
  
  • Age: reduced innate and adaptive immunity, reduced B-cell and T-cell receptor repertoires (‘immunosenescence’), thymic involution, fewer naïve T-cells, more memory T-cells
  • Obesity: large numbers of pro-inflammatory cells in fatty tissue, increased leptin secretion promoting decreased numbers of regulatory T-cells and regulatory T-cell function
  • Diabetes: strongly glycosylated Ig are more pro-inflammatory
  • Vascular disease: damaged endothelium (vasculopathy): risk of DIC and thrombotic events
  • Genetic background: HLA-type, polymorphisms in genes regulating inflammation, vitamin D binding protein variants (e.g. less free Vit D in black people), vitamin D-deficiency, and many more

Question 56

Vaccines: general information (COVID-19)

• Currently licenced vaccines in the UK
  
  • Astra Zeneca (… shots)
  • Pfizer/Biontech (… shots)
  • Moderna (… shots)
  • Johnson& Johnson (… shot)
• Following an extremely successful vaccine campaign in the UK
  
  • almost … million have been vaccinated fully
  • almost 40 million had one shot

Answer 56

• Currently licenced vaccines in the UK
  
  • Astra Zeneca (2 shots)
  • Pfizer/Biontech (2 shots)
  • Moderna (2 shots)
  • Johnson& Johnson (single shot)
• Following an extremely successful vaccine campaign in the UK
  
  • almost 25 million have been vaccinated fully
  • almost 40 million had one shot

Question 57

Vaccines: general information (COVID-19)

• Currently licenced vaccines in the UK
  
  • … … (2 shots)
  • Pfizer/Biontech (2 shots)
  • … (2 shots)
  • Johnson& Johnson (single shot)
• Following an extremely successful vaccine campaign in the UK
  
  • almost 25 million have been vaccinated fully
  • almost … million had one shot

Answer 57

• Currently licenced vaccines in the UK
  
  • Astra Zeneca (2 shots)
  • Pfizer/Biontech (2 shots)
  • Moderna (2 shots)
  • Johnson& Johnson (single shot)
• Following an extremely successful vaccine campaign in the UK
  
  • almost 25 million have been vaccinated fully
  • almost 40 million had one shot

Question 58

Vaccines: available COVID-19 vaccines

• (1) RNA/liposomes
  
  • …: BNT162b2 contains RNA that encodes an optimized full-length SARS-CoV-2 spike protein.
  • …: mRNA-1273 encodes a stabilized SARS-CoV-2 spike protein.
• (2) DNA/viral vectors
  
  • …: AZD122 contains a weakened version of a chimpanzee common cold adenovirus that contains DNA coding for the SARS-CoV-2 spike protein.
  • …: Ad26.COV2.S is an adenovirus vector (Ad26) that contains DNA encoding the SARS-CoV-2 spike protein
• Note: Vaccines may also use inactivated virus (Sinovac) but are not (yet) licenced in the UK

Answer 58

• (1) RNA/liposomes
  
  • Pfizer/Biontech: BNT162b2 contains RNA that encodes an optimized full-length SARS-CoV-2 spike protein.
  • Moderna: mRNA-1273 encodes a stabilized SARS-CoV-2 spike protein.
• (2) DNA/viral vectors
  
  • Oxford/Astra Zeneca: AZD122 contains a weakened version of a chimpanzee common cold adenovirus that contains DNA coding for the SARS-CoV-2 spike protein.
  • Johnson& Johnson: Ad26.COV2.S is an adenovirus vector (Ad26) that contains DNA encoding the SARS-CoV-2 spike protein
• Note: Vaccines may also use inactivated virus (Sinovac) but are not (yet) licenced in the UK

Question 59

Vaccines: available COVID-19 vaccines

• (1) RNA/liposomes
  
  • Pfizer/Biontech: BNT162b2 contains RNA that encodes an optimized full-length SARS-CoV-2 … protein.
  • Moderna: mRNA-1273 encodes a stabilized SARS-CoV-2 … protein.
• (2) DNA/viral vectors
  
  • Oxford/Astra Zeneca: AZD122 contains a weakened version of a chimpanzee common cold adenovirus that contains DNA coding for the SARS-CoV-2 … protein.
  • Johnson& Johnson: Ad26.COV2.S is an adenovirus vector (Ad26) that contains DNA encoding the SARS-CoV-2 … protein
• Note: Vaccines may also use … virus (Sinovac) but are not (yet) licenced in the UK

Answer 59

• (1) RNA/liposomes
  
  • Pfizer/Biontech: BNT162b2 contains RNA that encodes an optimized full-length SARS-CoV-2 spike protein.
  • Moderna: mRNA-1273 encodes a stabilized SARS-CoV-2 spike protein.
• (2) DNA/viral vectors
  
  • Oxford/Astra Zeneca: AZD122 contains a weakened version of a chimpanzee common cold adenovirus that contains DNA coding for the SARS-CoV-2 spike protein.
  • Johnson& Johnson: Ad26.COV2.S is an adenovirus vector (Ad26) that contains DNA encoding the SARS-CoV-2 spike protein
• Note: Vaccines may also use inactivated virus (Sinovac) but are not (yet) licenced in the UK

Question 60

Vaccines: RNA-based COVID-19 vaccines

• RNA vaccines use … RNA (mRNA) in order to achieve the production of relevant proteins of a … in host cells. Just as a reminder, RNA is composed of adenine (A), cytosine (C), guanine (G), and uracil (U). RNA vaccines are not integrated into the recipient’s …. In order to reach the inside of a cell, mRNA needs to be stabilised and packaged. Protein will be expressed in the injected tissues (i.e. muscle cells)
• Stability is achieved by
  • A specially modified Nucleotide positioned at the 5’ end (Cap)
  • A poly (A) tail
  • Composition and structure of the 3’ untranslated regions (3’UTR) contribute to intracellular mRNA stability.

Answer 60

• RNA vaccines use messenger RNA (mRNA) in order to achieve the production of relevant proteins of a pathogen in host cells. Just as a reminder, RNA is composed of adenine (A), cytosine (C), guanine (G), and uracil (U). RNA vaccines are not integrated into the recipient’s genome. In order to reach the inside of a cell, mRNA needs to be stabilised and packaged. Protein will be expressed in the injected tissues (i.e. muscle cells)
• Stability is achieved by
  • A specially modified Nucleotide positioned at the 5’ end (Cap)
  • A poly (A) tail
  • Composition and structure of the 3’ untranslated regions (3’UTR) contribute to intracellular mRNA stability.

Question 61

Vaccines: RNA-based COVID-19 vaccines

• RNA vaccines use messenger RNA (mRNA) in order to achieve the production of relevant proteins of a pathogen in host cells. Just as a reminder, RNA is composed of adenine (A), cytosine (C), guanine (G), and uracil (U). RNA vaccines are not integrated into the recipient’s genome. In order to reach the inside of a cell, mRNA needs to be stabilised and packaged. Protein will be expressed in the injected tissues (i.e. muscle cells)
• Stability is achieved by
  • A specially modified … positioned at the …’ end (Cap)
  • A poly (A) tail
  • Composition and structure of the …’ untranslated regions (3’UTR) contribute to intracellular mRNA stability.

Answer 61

• RNA vaccines use messenger RNA (mRNA) in order to achieve the production of relevant proteins of a pathogen in host cells. Just as a reminder, RNA is composed of adenine (A), cytosine (C), guanine (G), and uracil (U). RNA vaccines are not integrated into the recipient’s genome. In order to reach the inside of a cell, mRNA needs to be stabilised and packaged. Protein will be expressed in the injected tissues (i.e. muscle cells)
• Stability is achieved by
  • A specially modified Nucleotide positioned at the 5’ end (Cap)
  • A poly (A) tail
  • Composition and structure of the 3’ untranslated regions (3’UTR) contribute to intracellular mRNA stability.

Question 62

Vaccines: RNA-based COVID-19 vaccines

• RNA vaccines use messenger RNA (mRNA) in order to achieve the production of relevant proteins of a pathogen in host cells. Just as a reminder, RNA is composed of adenine (A), cytosine (C), guanine (G), and … RNA vaccines are not integrated into the recipient’s genome. In order to reach the inside of a cell, mRNA needs to be stabilised and packaged. Protein will be expressed in the injected tissues (i.e. muscle cells)
• Stability is achieved by
  • A specially modified Nucleotide positioned at the 5’ end (Cap)
  • A … (A) tail
  • Composition and structure of the 3’ … regions (3’UTR) contribute to intracellular mRNA stability.

Answer 62

• RNA vaccines use messenger RNA (mRNA) in order to achieve the production of relevant proteins of a pathogen in host cells. Just as a reminder, RNA is composed of adenine (A), cytosine (C), guanine (G), and uracil (U). RNA vaccines are not integrated into the recipient’s genome. In order to reach the inside of a cell, mRNA needs to be stabilised and packaged. Protein will be expressed in the injected tissues (i.e. muscle cells)
• Stability is achieved by
  • A specially modified Nucleotide positioned at the 5’ end (Cap)
  • A poly (A) tail
  • Composition and structure of the 3’ untranslated regions (3’UTR) contribute to intracellular mRNA stability.

Question 63

Vaccines: RNA-based COVID-19 vaccines

• Cell entry is achieved by packaging in …. These are fragile and may be damaged and destroyed by …
• In the beginning, the mRNA vaccines were treated with extreme care. Doses were drawn up immediately prior to … and a fair number of doses was discarded as a … e.g. after dropping syringes.
• In some countries the guidance for the Pfizer/Biontech vaccine, for example, has been adjusted a little bit, to the extent that vaccine doses can be drawn up centrally and transported by car to vaccine centres.

Answer 63

• Cell entry is achieved by packaging in liposomes. These are fragile and may be damaged and destroyed by shaking.
• In the beginning, the mRNA vaccines were treated with extreme care. Doses were drawn up immediately prior to administration and a fair number of doses was discarded as a precaution e.g. after dropping syringes.
• In some countries the guidance for the Pfizer/Biontech vaccine, for example, has been adjusted a little bit, to the extent that vaccine doses can be drawn up centrally and transported by car to vaccine centres.

Question 64

Vaccines: RNA-based COVID-19 vaccines

• Cell entry is achieved by packaging in …. These are … and may be … and destroyed by shaking.
• In the beginning, the mRNA vaccines were treated with extreme care. Doses were drawn up immediately prior to administration and a fair number of doses was discarded as a precaution e.g. after dropping syringes.
• In some countries the guidance for the Pfizer/Biontech vaccine, for example, has been adjusted a little bit, to the extent that vaccine doses can be drawn up centrally and transported by car to vaccine centres.

Answer 64

• Cell entry is achieved by packaging in liposomes. These are fragile and may be damaged and destroyed by shaking.
• In the beginning, the mRNA vaccines were treated with extreme care. Doses were drawn up immediately prior to administration and a fair number of doses was discarded as a precaution e.g. after dropping syringes.
• In some countries the guidance for the Pfizer/Biontech vaccine, for example, has been adjusted a little bit, to the extent that vaccine doses can be drawn up centrally and transported by car to vaccine centres.

Question 65

Vaccines: RNA-based COVID-19 vaccines

• Advantages:
  
  • …: no pathogen particles or inactivated pathogen, non-infectious, not integrated into host genome, RNA strand degraded once the protein is made.
  • …: reliable immune response
  • …: can be produced more rapidly, is standardised, improved response speed in emerging outbreaks
  • Appear to have fewer and/or less severe side-effects than … vaccines
• Disadvantages:
  
  • High cost (so far)
  • Logistic issues (low storage temperature, fragile)

Answer 65

• Advantages:
  
  • Safety: no pathogen particles or inactivated pathogen, non-infectious, not integrated into host genome, RNA strand degraded once the protein is made.
  • Efficacy: reliable immune response
  • Production: can be produced more rapidly, is standardised, improved response speed in emerging outbreaks
  • Appear to have fewer and/or less severe side-effects than conventional vaccines
• Disadvantages:
  
  • High cost (so far)
  • Logistic issues (low storage temperature, fragile)

Question 66

Vaccines: RNA-based COVID-19 vaccines

• Advantages:
  
  • Safety: no pathogen particles or inactivated pathogen, non-infectious, not integrated into host …, RNA strand … once the protein is made.
  • Efficacy: … immune response
  • Production: can be produced more rapidly, is standardised, improved response speed in emerging outbreaks
  • Appear to have fewer and/or less severe side-effects than conventional vaccines
• Disadvantages:
  
  • High … (so far)
  • Logistic issues (… storage …, F…)

Answer 66

• Advantages:
  
  • Safety: no pathogen particles or inactivated pathogen, non-infectious, not integrated into host genome, RNA strand degraded once the protein is made.
  • Efficacy: reliable immune response
  • Production: can be produced more rapidly, is standardised, improved response speed in emerging outbreaks
  • Appear to have fewer and/or less severe side-effects than conventional vaccines
• Disadvantages:
  
  • High cost (so far)
  • Logistic issues (low storage temperature, fragile)

Question 67

Long COVID

• Persistent symptoms beyond … weeks from acute disease
• May include extreme tiredness (fatigue), shortness of breath, chest pain or tightness, problems with memory and concentration (“brain fog”), and many additional symptoms (see e.g. NHS website*)
• May be linked to viral (antigen) …
• Bears striking similarity with ‘chronic … …’ (CFS)
• May result in part from … affection (‘Psychoneuroimmunology’)
• May result from persistent pro-inflammatory reprogramming of B-cells and T-cells with long-lasting effects on a range of organ systems
• Changes in gut microbiome/virome may also contribute

Answer 67

• Persistent symptoms beyond 12 weeks from acute disease
• May include extreme tiredness (fatigue), shortness of breath, chest pain or tightness, problems with memory and concentration (“brain fog”), and many additional symptoms (see e.g. NHS website*)
• May be linked to viral (antigen) persistence
• Bears striking similarity with ‘chronic fatigue syndrome’ (CFS)
• May result in part from CNS affection (‘Psychoneuroimmunology’)
• May result from persistent pro-inflammatory reprogramming of B-cells and T-cells with long-lasting effects on a range of organ systems
• Changes in gut microbiome/virome may also contribute

Question 68

Long COVID

• Persistent symptoms beyond 12 weeks from acute disease
• May include extreme tiredness (fatigue), shortness of breath, … pain or tightness, problems with memory and concentration (“… …”), and many additional symptoms (see e.g. NHS website*)
• May be linked to viral (antigen) persistence
• Bears striking similarity with ‘chronic fatigue syndrome’ (CFS)
• May result in part from CNS affection (‘…’)
• May result from persistent pro-… reprogramming of B-cells and T-cells with long-lasting effects on a range of … systems
• Changes in … microbiome/virome may also contribute

Answer 68

• Persistent symptoms beyond 12 weeks from acute disease
• May include extreme tiredness (fatigue), shortness of breath, chest pain or tightness, problems with memory and concentration (“brain fog”), and many additional symptoms (see e.g. NHS website*)
• May be linked to viral (antigen) persistence
• Bears striking similarity with ‘chronic fatigue syndrome’ (CFS)
• May result in part from CNS affection (‘Psychoneuroimmunology’)
• May result from persistent pro-inflammatory reprogramming of B-cells and T-cells with long-lasting effects on a range of organ systems
• Changes in gut microbiome/virome may also contribute

Question 69

Summary I - COVID-19 Lecture

• The immune response to COVID-19 is complex, but not necessarily more complex than that to other virus infections
• Both … and … immunity are important
• It may be that … immunity alone can clear the virus in … cases, which would explain why some individuals do not form antibodies or only have low antibody levels
• … immunity may be deficient in patients with a severe clinical course
• Drugs/agents that stimulate the early … immune response could be useful to prepare individuals for dealing with the infection (trained immunity)

Answer 69

• The immune response to COVID-19 is complex, but not necessarily more complex than that to other virus infections
• Both innate and adaptive immunity are important
• It may be that innate immunity alone can clear the virus in asymptomatic cases, which would explain why some individuals do not form antibodies or only have low antibody levels
• Innate immunity may be deficient in patients with a severe clinical course
• Drugs/agents that stimulate the early innate immune response could be useful to prepare individuals for dealing with the infection (trained immunity)

Question 70

Summary I - COVID-19 Lecture

• The immune response to COVID-19 is complex, but not necessarily more complex than that to other virus infections
• Both innate and adaptive immunity are important
• It may be that innate immunity alone can clear the virus in asymptomatic cases, which would explain why some individuals do not form … or only have low … levels
• Innate immunity may be deficient in patients with a severe clinical …
• Drugs/agents that stimulate the … innate immune response could be useful to prepare individuals for dealing with the infeciton (… …)

Answer 70

• The immune response to COVID-19 is complex, but not necessarily more complex than that to other virus infections
• Both innate and adaptive immunity are important
• It may be that innate immunity alone can clear the virus in asymptomatic cases, which would explain why some individuals do not form antibodies or only have low antibody levels
• Innate immunity may be deficient in patients with a severe clinical course
• Drugs/agents that stimulate the early innate immune response could be useful to prepare individuals for dealing with the infection (trained immunity)

Question 71

Summary II - COVID-19 Lecture

• Infection induces robust B and T-cell responses
• …-reactivity with … … coronaviruses exists but but we do not know if it is only protective or could also be harmful
• All licenced vaccines induce … B-cell and T- cell responses
• ….-reactivity is thought to explain why vaccines can achieve unexpected levels of immunity with just one shot
• Viral … so far do not appear to put vaccine success at risk
• New … accommodating … are being developed

Answer 71

• Infection induces robust B and T-cell responses
• Cross-reactivity with common cold coronaviruses exists but but we do not know if it is only protective or could also be harmful
• All licenced vaccines induce strong B-cell and T- cell responses
• Cross-reactivity is thought to explain why vaccines can achieve unexpected levels of immunity with just one shot
• Viral variants so far do not appear to put vaccine success at risk
• New vaccines accommodating variants are being developed

Question 72

Summary II - COVID-19 Lecture

• Infection induces robust B and T-cell responses
• Cross-reactivity with common cold coronaviruses exists but but we do not know if it is only protective or could also be harmful
• All licenced vaccines induce strong B-cell and T- cell responses
• Cross-reactivity is thought to explain why vaccines can achieve unexpected levels of immunity with just one shot
• Viral variants so far do not appear to put vaccine success at risk
• New vaccines accommodating variants are being developed

Answer 72

• Infection induces robust B and T-cell responses
• Cross-reactivity with common cold coronaviruses exists but but we do not know if it is only protective or could also be harmful
• All licenced vaccines induce strong B-cell and T- cell responses
• Cross-reactivity is thought to explain why vaccines can achieve unexpected levels of immunity with just one shot
• Viral variants so far do not appear to put vaccine success at risk
• New vaccines accommodating variants are being developed